Antiproliferative Activity of Antibiotics through DNA Binding Mechanism: Evaluation and Molecular Docking Studies

The antiproliferative activity of three antibiotics clinically use, was studied through DNA inhibition mechanisms, ex vivo, in silico and in vitro. The ex vivo interaction of DNA with ciprofloxacin hydrochloride (CIP center dot HCl), penicillin G sodium salt (PEN center dot Na), and tetracycline hydrochloride (TC center dot HCl) was determined by UV-Vis spectra and viscosity measurements. Furthermore, their binding constants (K-b) toward CT-DNA were calculated (K-b = (2.8 +/- 0.6) x 10(4) (CIP center dot HCl), (0.4 +/- 0.1) x 10(4) (PEN center dot Na) and (6.9 +/- 0.3) x 10(4) (TC center dot HCl) M-1). Docking studies on the binding interactions of antibiotics with DNA were performed to rationalize the ex vivo results. The in vitro antiproliferative activity of the antibiotics was evaluated against human breast adenocarcinoma (MCF-7) cells (IC50 values: 417.4 +/- 28.2 (CIP center dot HCl), >2000 (PEN center dot Na) and 443.1 +/- 17.2 (TC center dot HCl) mu M). Cell cycle arrest studies confirmed the apoptotic type of MCF-7 cells. The toxicity of the studied agents was in vitro tested against human fetal lung fibroblast cells (MRC-5). The results are compared with the corresponding one for doxorubicin (DOX). Despite their low binding affinity to DNA (K-b) or their different mode of interaction, TC center dot HCl (anthracycline) or CIP center dot HCl (quinolones), exhibit notable antiproliferative activity and low toxicity.